Substituted bicyclic and tricyclic thrombin receptor antagonists
View Patent ↗Substituted bicyclic and tricyclic modified himbacine derivative of the formula: or a pharmaceutically acceptable salt or solvate of said compound wherein represents an optional double bond and wherein E n , F n , G n , Z n , J n , X, R 3 , R 9 , R 10 , R 11 , R 32 , R 33 , B and Het are herein defined are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds. Combination therapy with other agents is also claimed.
1. A compound of Formula IK or Formula IIK
or a pharmaceutically acceptable salt thereof
wherein:
Het is a pyridyl group wherein the pyridyl group is attached to B by a carbon atom ring member, and wherein the pyridyl group is substituted by 1 to 4 moieties, W, wherein each W is independently selected from the group consisting of:
hydrogen, alkyl, aryl or aryl substituted by 1 to 3 substituents independently selected from the group consisting of alkyl, halogen, alkoxy,
—CN, —CF 3 , —OCF 3 or —OH;
R 1 is hydrogen, alkyl, fluroalkyl, difluroralkyl or trifluroralkyl;
R 2 is hydrogen, alkyl, fluroalkyl, difluroralkyl or trifluroralkyl;
R 9 is hydrogen;
R 10 and R 11 are H or alkyl;
R 32 and R 33 are H or alkyl.
2. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 32 and R 33 , which can be the same or different, are each alkyl.
3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 32 and R 33 are each methyl.
4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Q is
5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein W is phenyl, which is unsubstituted or substituted by a group selected from the group consisting of halogen or —CN.
6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 9 , R 10 and R 11 are hydrogen.
7. A compound of the formula or a pharmaceutically acceptable salt thereof, which is:
8. A pharmaceutical composition comprising an effective amount of at least one compound of claim 1 and a pharmaceutically acceptable carrier.
9. A compound of claim 1 or a pharmaceutically acceptable salt thereof in purified form.
10. A compound of claim 1 or a pharmaceutically acceptable salt thereof in isolated form.